Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Oliveira, Juliana Sorraila de lattes
Orientador(a): Andrade, Cinthia Melazzo de lattes
Banca de defesa: Cardoso, Andréia Machado lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Departamento: Bioquímica
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/18594
Resumo: Alzheimer's Disease (AD) is considered one of the main causes of dementia. Thus, the research for new therapeutic interventions for treatment is of utmost importance. Berberine (BRB) is an isoquinoline alkaloid that has multiple pharmacological actions including antioxidant, anti-inflammatory and neuroprotective properties. Preclinical studies have suggested their use in neurodegenerative disorders, including AD. Thus, the aim of this study was designed to investigate the effects of BRB on behavioral tests, acetylcholinesterase (AChE) activity and cell death in rat model of streptozotocin (STZ)-induced experimental dementia of Alzheimer’s type. Sixty Adult male Wistar rats were treated with BRB or saline orally once daily for 21 days and then bilaterally injected with a single intracerebroventricular-streptozotocin (ICV-STZ) (3 mg/kg, 5μL). The rats were divided into six groups (n = 10): Group I: control group; group II received BRB 50 mg/kg, group III received BRB 100 mg/kg, group IV received STZ, group V received STZ + BRB 50 mg/kg and group VI received STZ + BRB 100 mg/kg. The behavior was assessed through the Water Maze test and elevated plus maze. Behavioral parameters were assessed through Morris water maze and elevated plus maze tests. Cell death analysis and AChE activity were performed on cerebral cortex and hippocampus. The results revealed that BRB prevented memory loss, anxiogenic behavior, elevation in AChE activity and cell death induced by ICV-STZ, thereby demonstrating significant neurobehavioral and neuroprotective effects. In conclusion, our results suggest that BRB may be a potential candidate for adjuvant treatment of AD.
id UFSM_5590476f468bd8026118ffa6262c735d
oai_identifier_str oai:repositorio.ufsm.br:1/18594
network_acronym_str UFSM
network_name_str Biblioteca Digital de Teses e Dissertações do UFSM
repository_id_str
spelling 2019-10-15T15:29:49Z2019-10-15T15:29:49Z2016-07-18http://repositorio.ufsm.br/handle/1/18594Alzheimer's Disease (AD) is considered one of the main causes of dementia. Thus, the research for new therapeutic interventions for treatment is of utmost importance. Berberine (BRB) is an isoquinoline alkaloid that has multiple pharmacological actions including antioxidant, anti-inflammatory and neuroprotective properties. Preclinical studies have suggested their use in neurodegenerative disorders, including AD. Thus, the aim of this study was designed to investigate the effects of BRB on behavioral tests, acetylcholinesterase (AChE) activity and cell death in rat model of streptozotocin (STZ)-induced experimental dementia of Alzheimer’s type. Sixty Adult male Wistar rats were treated with BRB or saline orally once daily for 21 days and then bilaterally injected with a single intracerebroventricular-streptozotocin (ICV-STZ) (3 mg/kg, 5μL). The rats were divided into six groups (n = 10): Group I: control group; group II received BRB 50 mg/kg, group III received BRB 100 mg/kg, group IV received STZ, group V received STZ + BRB 50 mg/kg and group VI received STZ + BRB 100 mg/kg. The behavior was assessed through the Water Maze test and elevated plus maze. Behavioral parameters were assessed through Morris water maze and elevated plus maze tests. Cell death analysis and AChE activity were performed on cerebral cortex and hippocampus. The results revealed that BRB prevented memory loss, anxiogenic behavior, elevation in AChE activity and cell death induced by ICV-STZ, thereby demonstrating significant neurobehavioral and neuroprotective effects. In conclusion, our results suggest that BRB may be a potential candidate for adjuvant treatment of AD.A Doença de Alzheimer (DA) é considerada a principal causa de demência no mundo. Assim, a busca por novas intervenções terapêuticas para seu tratamento é de extrema importância. A berberina (BRB), é um alcalóide isoquinolina que apresenta múltiplas ações farmacológicas, tais como antioxidante, anti-inflamatória e neuroprotetora. Estudos pré-clínicos vem sugerindo a sua utilização em patologias neurodegenerativas, entre elas a DA. Deste modo, o objetivo deste estudo foi investigar os efeitos da BRB sobre a aprendizagem e memória espacial, comportamento de ansiedade, atividade da acetilcolinesterase (AChE) e morte celular em um modelo de demência esporádica do tipo Alzheimer induzido por estreptozotocina (STZ) em ratos. Foram utilizados 60 ratos wistar machos, distribuídos em seis grupos (n= 10): Controle, BRB 50 mg/kg, BRB 100 mg/kg, STZ + salina, STZ + BRB 50 mg/kg, STZ + BRB 100 mg/kg. Os ratos STZ receberam uma injeção de STZ (3 mg/kg, 5 μL) intracerebroventricular (ICV) e foram tratados com BRB ou salina via oral. Os animais controle receberam ICV-salina (5 μL) e foram tratados com as mesmas soluções. O comportamento foi avaliado através dos testes de Water Maze e labirinto em cruz elevada. As análises de morte celular e a atividade da AChE foram realizadas em córtex cerebral e hipocampo. Os resultados revelaram que BRB foi capaz de prevenir a perda de memória, o comportamento ansiogênico, o aumento na atividade da AChE e a morte celular induzida por ICVSTZ, demonstrando um importante efeito neuroprotetor. Portanto, sugere-se que este composto pode ser um potencial candidato para o tratamento coadjuvante da DA.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDoença neurodegenerativaSistema colinérgicoDemência esporádicaMorte celular neuronalNeurodegenerative diseaseCholinergic systemSporadic dementiaNeuronal cell deathCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo AlzheimerEffect of Berberine on behavioral tests and Acetylcholinesterase activity in rats submitted sporadic dementia of Alzheimer's typeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAndrade, Cinthia Melazzo dehttp://lattes.cnpq.br/2886709251370905Abdalla, Fátima Huseinhttp://lattes.cnpq.br/7953691285006874Cardoso, Andréia Machadohttp://lattes.cnpq.br/0690875690674360http://lattes.cnpq.br/8100915855340544Oliveira, Juliana Sorraila de200800000002600e0391f7d-99bf-47cd-a356-a3994d247daad243f8da-c6ac-45fa-9cfe-08b3d62548a984b7ca14-85c1-4d33-9f32-6222f96eff9479fe0b9c-bac0-4cdf-a37d-1e3ef32c538dreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdfDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdfDissertação de Mestradoapplication/pdf2627271http://repositorio.ufsm.br/bitstream/1/18594/1/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdfe03013a039a4a9a490c205de8e7ab904MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/18594/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/18594/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53TEXTDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.txtDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.txtExtracted texttext/plain120707http://repositorio.ufsm.br/bitstream/1/18594/4/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.txt409e1099840cbae2e125d3e0475df078MD54THUMBNAILDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.jpgDIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.jpgIM Thumbnailimage/jpeg4508http://repositorio.ufsm.br/bitstream/1/18594/5/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.jpg78f72c6f7ab6f4bf87a500539d1ecd28MD551/185942019-10-16 03:00:37.879oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-10-16T06:00:37Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
dc.title.alternative.eng.fl_str_mv Effect of Berberine on behavioral tests and Acetylcholinesterase activity in rats submitted sporadic dementia of Alzheimer's type
title Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
spellingShingle Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
Oliveira, Juliana Sorraila de
Doença neurodegenerativa
Sistema colinérgico
Demência esporádica
Morte celular neuronal
Neurodegenerative disease
Cholinergic system
Sporadic dementia
Neuronal cell death
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
title_full Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
title_fullStr Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
title_full_unstemmed Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
title_sort Efeito da Berberina sobre testes comportamentais e atividade da Acetilcolinesterase em ratos submetidos a um modelo de demência esporádica do tipo Alzheimer
author Oliveira, Juliana Sorraila de
author_facet Oliveira, Juliana Sorraila de
author_role author
dc.contributor.advisor1.fl_str_mv Andrade, Cinthia Melazzo de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2886709251370905
dc.contributor.advisor-co1.fl_str_mv Abdalla, Fátima Husein
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/7953691285006874
dc.contributor.referee1.fl_str_mv Cardoso, Andréia Machado
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0690875690674360
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8100915855340544
dc.contributor.author.fl_str_mv Oliveira, Juliana Sorraila de
contributor_str_mv Andrade, Cinthia Melazzo de
Abdalla, Fátima Husein
Cardoso, Andréia Machado
dc.subject.por.fl_str_mv Doença neurodegenerativa
Sistema colinérgico
Demência esporádica
Morte celular neuronal
topic Doença neurodegenerativa
Sistema colinérgico
Demência esporádica
Morte celular neuronal
Neurodegenerative disease
Cholinergic system
Sporadic dementia
Neuronal cell death
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Neurodegenerative disease
Cholinergic system
Sporadic dementia
Neuronal cell death
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Alzheimer's Disease (AD) is considered one of the main causes of dementia. Thus, the research for new therapeutic interventions for treatment is of utmost importance. Berberine (BRB) is an isoquinoline alkaloid that has multiple pharmacological actions including antioxidant, anti-inflammatory and neuroprotective properties. Preclinical studies have suggested their use in neurodegenerative disorders, including AD. Thus, the aim of this study was designed to investigate the effects of BRB on behavioral tests, acetylcholinesterase (AChE) activity and cell death in rat model of streptozotocin (STZ)-induced experimental dementia of Alzheimer’s type. Sixty Adult male Wistar rats were treated with BRB or saline orally once daily for 21 days and then bilaterally injected with a single intracerebroventricular-streptozotocin (ICV-STZ) (3 mg/kg, 5μL). The rats were divided into six groups (n = 10): Group I: control group; group II received BRB 50 mg/kg, group III received BRB 100 mg/kg, group IV received STZ, group V received STZ + BRB 50 mg/kg and group VI received STZ + BRB 100 mg/kg. The behavior was assessed through the Water Maze test and elevated plus maze. Behavioral parameters were assessed through Morris water maze and elevated plus maze tests. Cell death analysis and AChE activity were performed on cerebral cortex and hippocampus. The results revealed that BRB prevented memory loss, anxiogenic behavior, elevation in AChE activity and cell death induced by ICV-STZ, thereby demonstrating significant neurobehavioral and neuroprotective effects. In conclusion, our results suggest that BRB may be a potential candidate for adjuvant treatment of AD.
publishDate 2016
dc.date.issued.fl_str_mv 2016-07-18
dc.date.accessioned.fl_str_mv 2019-10-15T15:29:49Z
dc.date.available.fl_str_mv 2019-10-15T15:29:49Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/18594
url http://repositorio.ufsm.br/handle/1/18594
dc.language.iso.fl_str_mv por
language por
dc.relation.cnpq.fl_str_mv 200800000002
dc.relation.confidence.fl_str_mv 600
dc.relation.authority.fl_str_mv e0391f7d-99bf-47cd-a356-a3994d247daa
d243f8da-c6ac-45fa-9cfe-08b3d62548a9
84b7ca14-85c1-4d33-9f32-6222f96eff94
79fe0b9c-bac0-4cdf-a37d-1e3ef32c538d
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
dc.publisher.initials.fl_str_mv UFSM
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Bioquímica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações do UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Biblioteca Digital de Teses e Dissertações do UFSM
collection Biblioteca Digital de Teses e Dissertações do UFSM
bitstream.url.fl_str_mv http://repositorio.ufsm.br/bitstream/1/18594/1/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf
http://repositorio.ufsm.br/bitstream/1/18594/2/license_rdf
http://repositorio.ufsm.br/bitstream/1/18594/3/license.txt
http://repositorio.ufsm.br/bitstream/1/18594/4/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.txt
http://repositorio.ufsm.br/bitstream/1/18594/5/DIS_PPGCBBT_2016_OLIVEIRA_JULIANA.pdf.jpg
bitstream.checksum.fl_str_mv e03013a039a4a9a490c205de8e7ab904
4460e5956bc1d1639be9ae6146a50347
2f0571ecee68693bd5cd3f17c1e075df
409e1099840cbae2e125d3e0475df078
78f72c6f7ab6f4bf87a500539d1ecd28
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
_version_ 1793240124431007744